The purpose of this study is to analyze the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein stent and 125I implantation for the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma. Fifty-six patients from our department diagnosed with advanced hepatocellular carcinoma with PVTT between January 2008 and December 30, 2010 were divided into two groups. Patients in Group A were treated with TACE and portal vein stent; Patients in Group B were treated with TACE, portal vein stent, and 125I implantation. The success rate of TACE with portal vein stent and 125I implantation was 100%, with no severe surgery-related complications. After an 8-month follow-up, the total clinical benefit rates were 56.7 and 88.5% for groups A and B, respectively (p ＜ 0.05). The median survival times (mOS) for the two groups were 5.7 months and 8.9 months, respectively (p ＜ 0.05). The median time of progression (mTTP) of the two groups were 5.3 months and 7.9 months, respectively (p ＜ 0.05). The 2-, 6-, 8-, 12-, and 18-mouth patency rates in Group A were 100, 93.3, 83.3, 53.3, and 36.6%. Those in Group B were 100, 100, 92.3, 84.6, and 80.7%. The 2-, 6-, and 8-month patency rates showed no statistical differences (p ＞ 0.05), but the 12- and 18-month rates did (p ＜ 0.05). Our results suggest that TACE combined with portal vein stent and 125I implantation are both safe and effective, and 125I implantation can further postpone the restenosis of the portal vein effectively.